Medication Development

Question 1

Define what is meant by a clinical trial

Answer 1

A clinical trial is any form of planned experiment which involved patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition

Question 2

Explain the disadvantages of non-randomised clinical trials

Answer 2

Non-randomised clinical trials:

• may lead to allocation bias but patient, clinician or investigator
• may lead to confounding- both known and unknown

Question 3

Outline the steps involved in a randomised controlled trail (RCT)

Answer 3

1. Definition of factors:
   - disease of interest
   - treatments to be compared
   - outcomes to be measured
   - possible bias and confounders
   - patients eligible for trial
   - patients to be excluded from the trial
2. Conduct of the trial:
   - Source of eligible patients
   - Invite eligible patients to trial
   - Consent patients willing to be in the trial
   - Allocate patients to the treatments fairly
   - Follow-up participants in identical ways
   - Minimise losses to follow-up
   - Maximise compliance with treatments
3. Comparison of outcomes
   - Observed difference in outcome between two treatment groups?
   - Could this have arisen by chance (stat. sig.)
   - How big is the observed difference (clinically important)
   - Observed difference attributable to the treatments compared in the trial?

Question 4

Describe some features of an “Ideal Outcome”

Answer 4

Appropriate and relevant 
Valid and attributable 
Sensitive and specific 
Reliable and robust 
Simple and sustainable 
Cheap and timely

Question 5

Discuss the advantages of ‘random allocation’ to minimise confounding and bias in the estimation of treatment effects

Answer 5

Minimises allocation bias: each participant has equal chance of being allocated to each treatment) and confounding factors: known and unknown, treatment grouped likely to be similar in size and characteristics by chance

Question 6

Discuss the advantages of ‘blinding’ to minimise confounding and bias in the estimation of treatment effects

Answer 6

Without blinding:

Patient may alter their behaviour
Clinician may alter their treatment, care, interest
Investigator may alter their approach when measuring/assessing outcomes

Question 7

Describe the ‘placebo effect’

Answer 7

Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness, and indeed the illness itself, may be improved by a feeling that something is being done about it

Question 8

Describe what a ‘placebo’ is

Answer 8

An inert substance made to appear identical in every way to the active formulation with which it is being compared

Question 9

Describe how ‘placebo’ addresses ‘placebo effect’

Answer 9

The aim of a placebo is to cancel out any placebo effect that may exist in the active treatment

Question 10

Discuss how to deal with ‘losses to follow up’

Answer 10

Analysis of outcomes should take into account that you can’t always have 100% follow-up
Explanatory or pragmatic trials
Should be pragmatic

Question 11

Discuss how to deal with ‘non-compliance’

Answer 11

Analysis of outcomes should take into account that you can’t always have 100% compliance
Explanatory or pragmatic trials
Should be pragmatic

Question 12

Differentiate between ‘explanatory’ and ‘pragmatic’ trials

Answer 12

Explanatory trials:

• As-treated- analyses only those who completed follow-up and complied with treatments
• Lose the effects of randomisation
• Larger sizes of effect

Pragmatic trials:

• Intention to treat- analyses according to the original allocation to treatment groups (regardless of follow-up or compliance)
• Compares the likely effect of using the treatments in routine clinical practice
• Preserves randomisation
• Smaller and more realistic size of effect

Question 13

Explain the meaning of the term ‘intention-to-treat’ analysis

Answer 13

Analysis that is based on the original allocations to treatment group regardless of follow-up or compliance

Question 14

Discuss the ethical principles involved in medical research involving human subjects

Answer 14

“Health of my patient will be my first consideration” Declaration of Helsinki

Collective ethics:
-All patients should have treatments that are properly tested for efficacy and safety

Individual ethics:

• Beneficence (not guarantee benefit)
• Non-maleficence (not cause harm)
• Autonomy (allocate by chance)
• Justice

Question 15

Describe the issues that should be considered for a clinical trial to be regarded as “ethical”

Answer 15

Clinical equipoise - uncertainty or ignorance about the better treatment or intervention

Scientifically robust- valid questions, appropriate study, justify placebo

Ethical recruitment- should not include participants from communities that are unlikely to benefit or at high risk of harm or those likely to be excluded from the analysis, those who cannot give valid consent

Valid consent - informed (written, verbal, cooling off, opt out), competent decision maker, legitimate authoriser

Voluntariness - decision free from coercion or manipulation

Question 16

Describe the role and function of a Research Ethic Committee

Answer 16

Ensure the dignity, rights and safety of participants much be primary consideration in any research study

Focus on:
Scientific design and conduct
Recruitment of participants
Care and protection of research participants
Protection of participant confidentiality
Informed consent process
Community considerations

Question 17

For what reasons might a patient not comply to their allocated treatment?

Answer 17

Mis-understood instructions 
May not like the treatment 
Side effects 
May prefer another treatment 
May not have time/ cba to take their treatment